Application of sequential factorial design and orthogonal array composite design (OACD) to study combination of 5 prostate cancer drugs

Prostate cancer is one of the most common cancers among men in the United States. It is also a major leading cause of cancer death among men of all races. In order to treat prostate cancer, drug combinations are often applied. Drug combinations target at different pathways of cells can potentially lead to higher efficacy and lower toxicity due to drug synergy. In this paper, we sequentially applied a two-level design and a follow-up orthogonal array composite design (OACD) to investigate combinations of five anti-cancer drugs, namely, doxorubicin, docetaxel, paclitaxel, cis-dichlorodiamine platinum and dihydroartemisinin. Our initial screening using a two-level full factorial design identified doxorubicin and docetaxel as the most significant drugs. A follow-up experiment with an OACD revealed more complicated drug interactions among these 5 anti-cancer drugs. Quadratic effects of doxorubicin and paclitaxel appeared to be significant. A further investigation on contour plots of all the two-drug pairs indicated that combination of doxorubicin and docetaxel are the most effective companion, while the combination of cis-dichlorodiamine platinum and dihydroartemisinin showed unknown antagonistic effects which diminished the individual drug anti-cancer efficacy. These observations have significant practical implications in the understanding of anti-cancer drug mechanism that can facilitate clinical practice of better drug combinations.     

Evaluation of ORAC methodologies in determination of antioxidant capacity of binary combinations of quercetin and 3-(3,4,5-trihydroxybenzoyl) coumarin derivatives

Antioxidant capacity is used to refer to ability of compounds to react with free radicals, it is also described as ability to inhibit oxidation processes. There are different methods that evaluate the antioxidant capacity of compounds of natural origin or extracts. ORAC methodologies measure the ability to transfer hydrogen atoms to RO·/ROO· radicals generated by the AAPH thermolysis, in presence of a probe that accounts for oxidation of antioxidant. Despite extensive use of these methods to assess antioxidant capacity, they have been questioned by type of radical generated and information they can deliver, especially if it is a mixture of compounds. In this work, antioxidant capacity of binary combinations of quercetin with synthetic 3-phenylcoumarins was evaluated through ORAC-FL, PGR and quantification techniques after oxidation kinetics via free radicals, through HPLC. It was found through ORAC-FL that derived 3-(3,4,5-trihydroxybenzoyl) coumarin have greater antioxidant capacity than Trolox: 1 < 2 < 3 < quercetin. Determination of ORAC-FL indices of combination showed an antagonistic effect among the antioxidants. Also, ORAC-PGR method did not allow determination of antioxidant capacity of compounds, separately, indicated high reactivity of compounds. However, unusual behaviors were observed in combinations, unable to explain antagonistic effect observed in ORAC-FL. HPLC oxidation kinetics analysis showed that in the combination the consumption of the most reactive antioxidant dominated the antioxidant capacity and followed a similar trend as observed by ORAC-FL. Therefore, ORAC methodologies would not be useful in characterizing antioxidant capacity of mixture in relation to reactivity of metabolites present therein, but in relation to amount of hydroxyl groups available.     

Cancer cells undergoing epigenetic transition show short-term resistance and are transformed into cells with medium-term resistance by drug treatment

To elucidate the epigenetic mechanisms of drug resistance, epigenetically reprogrammed H460 cancer cells (R-H460) were established by the transient introduction of reprogramming factors. Then, the R-H460 cells were induced to differentiate by the withdrawal of stem cell media for various durations, which resulted in differentiated R-H460 cells (dR-H460). Notably, dR-H460 cells differentiated for 13 days (13dR-H460 cells) formed a significantly greater number of colonies showing drug resistance to both cisplatin and paclitaxel, whereas the dR-H460 cells differentiated for 40 days (40dR-H460 cells) lost drug resistance; this suggests that 13dR-cancer cells present short-term resistance (less than a month). Similarly, increased drug resistance to both cisplatin and paclitaxel was observed in another R-cancer cell model prepared from N87 cells. The resistant phenotype of the cisplatin-resistant (CR) colonies obtained through cisplatin treatment was maintained for 2–3 months after drug treatment, suggesting that drug treatment transforms cells with short-term resistance into cells with medium-term resistance. In single-cell analyses, heterogeneity was not found to increase in 13dR-H460 cells, suggesting that cancer cells with short-term resistance, rather than heterogeneous cells, may confer epigenetically driven drug resistance in our reprogrammed cancer model. The epigenetically driven short-term and medium-term drug resistance mechanisms could provide new cancer-fighting strategies involving the control of cancer cells during epigenetic transition.Subject terms: Tumour heterogeneity, Epigenetics     

Evaluation of the synergetic radio-chemotherapy effects of the radio labelled cisplatin for the treatment of glioma

The proposal of this work was to investigate the effect of the radioactive (NH₃)₂PtCl₂, cis-diamminedichloroplatinum (II) or CDDP* on malignant glioma cells and verify if the low-dose continuous internal radio-chemotherapy would be able to produce additive effects. The antitumoral activity of CDDP* and the non labeled cisplatin, CDDP, were evaluated in glioblastoma. Cisplatin was cytotoxic for glioblastoma cells in a dose dependent manner. Treatment with CDDP*, (IC₅₀ = 1.75 ± 0.07 μM), proved to be more potent than using just CDDP, (IC₅₀ = 4.96 ± 0.40 μM). These results suggest that cisplatin is a very potent radiosensitizer evoking a supra additive effect. Internal radio-chemotherapy treatment based on CDDP* may be useful alternative to reduce the drug concentration required for effective inhibition of glioblastoma growth.     

Development of a blood-brain barrier model in a membrane-based microchip for characterization of drug permeability and cytotoxicity for drug screening

Since most of the central nervous system (CNS) drug candidates show poor permeability across the blood-brain barrier (BBB), development of a reliable platform for permeability assay will greatly accelerate drug discovery. Herein, we constructed a microfluidic BBB model to mimic drug delivery into the brain to induce cytotoxicity at target cells. To reconstitute the in vivo BBB properties, human cerebral microvessel endothelial cells (hCMEC/D3) were dynamically cultured in a membrane-based microchannel. Sunitinib, a model drug, was then delivered into the microchannel and forced to permeate through the BBB model. The permeated amount was directly quantified by an electrospray ionization quadrupole time-of-flight mass spectrometer (ESI-Q-TOF MS) after on-chip SPE (μSPE) pretreatment. Moreover, the permeated drug was incubated with glioma cells (U251) cultured inside agarose gel in the downstream to investigate drug-induced cytotoxicity. The resultant permeability of sunitinib was highly correlated with literature reported value, and it only required 30 min and 5 μL of sample solution for each permeation experiment. Moreover, after 48 h of treatment, the survival rate of U251 cells cultured in 3D scaffolds was nearly 6% higher than that in 2D, which was in accordance with the previously reported results. These results demonstrate that this platform provides a valid tool for drug permeability and cytotoxicity assays which have great value for the research and development of CNS drugs.     

Photodynamic Efficacy of Cercosporin in 3D Tumor Cell Cultures

In the present work, we study the photodynamic action of cercosporin (cerco), a naturally occurring photosensitizer, on human cancer multicellular spheroids. U87 spheroids exhibit double the uptake of cerco than T47D and T98G spheroids as shown by flow cytometry on the single cell level. Moreover, cerco is efficiently internalized by cells throughout the spheroid as shown by confocal microscopy, for all three cell lines. Despite their higher cerco uptake, U87 spheroids show the least vulnerability to cerco-PDT, in contrast to the other two cell lines (T47D and T98G). While 300 μm diameter spheroids consistently shrink and become necrotic after cerco PDT, bigger spheroids (>500 μm) start to regrow following blue-light PDT and exhibit high viability. Cerco-PDT was found to be effective on bigger spheroids reaching 1mm in diameter especially under longer exposure to yellow light (~590 nm). In terms of metabolism, T47D and T98G undergo a complete bioenergetic collapse (respiration and glycolysis) as a result of cerco-PDT. U87 spheroids also experienced a respiratory collapse following cerco-PDT, but retained half their glycolytic activity.     

Analysis of U87 glioma cells by dielectrophoresis

Glioblastoma multiforme is the most aggressive and invasive brain cancer consisting of genetically and phenotypically altering glial cells. It has massive heterogeneity due to its highly complex and dynamic microenvironment. Here, electrophysiological properties of U87 human glioma cell line were measured based on a dielectrophoresis phenomenon to quantify the population heterogeneity of glioma cells. Dielectrophoretic forces were generated using a gold-microelectrode array within a microfluidic channel when 3 V_pp and 100, 200, 300, 400, 500 kHz, 1, 2, 5, and 10 MHz frequencies were applied. We analyzed the dielectrophoretic behavior of 500 glioma cells, and revealed that the crossover frequency of glioma cells was around 140 kHz. A quantifying dielectrophoretic movement of the glioma cells exhibited three distinct glioma subpopulations: 50% of the glioma cells experienced strong, 30% of the cells were spread in the microchannel by moderate, and the rest of the cells experienced very weak positive dielectrophoretic forces. Our results demonstrated the dielectrophoretic spectra of U87 glioma cell line. Dielectrophoretic responses of glioma cells linked population heterogeneity to membrane properties of glioma cells rather than their size distribution in the population.     

Ruthenacarborane and Quinoline: A Promising Combination for the Treatment of Brain Tumors

Gliomas and glioblastomas are very aggressive forms of brain tumors, prone to the development of a multitude of resistance mechanisms to therapeutic treatments, including cytoprotective autophagy. In this work, we investigated the role and mechanism of action of the combination of a ruthenacarborane derivative with 8-hydroxyquinoline (8-HQ), linked via an ester bond (complex 2), in rat astrocytoma C6 and human glioma U251 cells, in comparison with the two compounds alone, i.e., the free carboxylic acid (complex 1) and 8-HQ, and their non-covalent combination ([1 + 8-HQ], in 1:1 molar ratio). We found that only complex 2 was able to significantly affect cellular viability in glioma U251 cells (IC₅₀ 11.4 μM) via inhibition of the autophagic machinery, most likely acting at the early stages of the autophagic cascade. Contrary to 8-HQ alone, complex 2 was also able to impair cellular viability under conditions of glucose deprivation. We thus suggest different mechanisms of action of ruthenacarborane complex 2 than purely organic quinoline-based drugs, making complex 2 a very attractive candidate for evading the known resistances of brain tumors to chloroquine-based therapies.     

Separation through liquid–liquid extraction and spectrophotometric determination of U(VI) with the ortho-aminophenol reagent

The extractive properties of the ortho-aminophenol reagent upon U(VI) were investigated in two solvents: 4-chlor-acetophenone and acetylacetone, in a water-organic solvent system. The method here proposed is based on the complexation reaction of the uranyl ion, UO₂ ²⁺, with ortho-aminophenol dissolved in 4-chlor-acetophenone, at room temperature, over a pH interval = 4–6, followed by spectro-photometry of the organic phase, involving measuring of absorbancy at 569.6 nm. The Beer law is valid over the 1–12 μg U(VI)/mL concentration interval, with molar absorbtivity ε_max = 4.3 × 10⁵ mol⁻¹ cm² and Sandell sensitivity = 0.0526 μg cm⁻². The structure, stability and solubility of the formed complex was studied by UV–VIS and IR spectrometry, diffractometry and scanning electron microscopy. The mixed complex formed between the uranyl ion and the ortho-aminophenol dissolved in 4-chlor-acetophenone, [UO₂.(L)₂.(S)₄], is characterized by the following parameters: metal/ligand combination ratio: M/L = 1/2, stability constant β = 2.06 × 10⁶, distribution coefficient D = 66.56 (V_org = V_aq), percentage extraction E% = 98.52, and recovery factor, R%, ranging between 99.48 and 99.85%.     

SENSITIVITY OF ACTIVATED MURINE PERITONEAL MACROPHAGES TO PHOTODYNAMIC KILLING WITH BENZOPORPHYRIN DERIVATIVE

Abstract— This study compared the ability of highly purified resting and activated DBA/2 mouse peritoneal macrophages to survive treatment with the photosensitizer benzoporphyrin derivative (BPD, verteporfin) and light. Culture of macrophages with recombinant murine interferon-γ (rIFN-γ, 100 U/mL) for 72 h imparted a phenotypic and functional activation by dramatically increasing cell surface expression of major histocompatibility complex Class II (Ia) molecules and the formation of nitric oxide. The rIFN-γ-activated macrophages were significantly (P < 0.05) more sensitive (lethal dose to cause a 50% reduction in cell survival, LD₅₀= 14.4 ± 1.1 ng/mL) to photodynamic killing with BPD and light (10 J/cm²) than cells (LD₅₀= 18.2 ± 2.0 ng/mL) cultured in medium alone. In contrast, macrophages treated with different concentrations of bacterial lipopolysaccharide (LPS) were as resistant or more resistant to photodynamic killing than cells cultured in medium alone. No cytotoxic effect of BPD was detected in cultures containing the drug but protected from light. Comparable amounts of BPD were taken up in vitro by unactivated and rIFN-γ-activated macrophages, as detected by flow cytometric analysis. However, cells cultured with LPS (10 μg/mL) took up more BPD than macrophages cultured in medium alone or with rIFN-γ. The DBA/2 P815 mastocytoma cells took up greater amounts of the drug and were subsequently more vulnerable to treatment with BPD and light (LD₅₀= 6.9 ng/mL) than macrophages cultured under any condition. The explanation for the increased vulnerability of rIFN-γ-activated macrophages and the greater resistance of LPS-activated macrophages, relative to medium-cultured macrophages, to photodynamic killing with BPD is uncertain. However, the increased susceptibility of macrophages, activated with the immunomodulatory cytokine IFN-γ, to treatment with BPD and light might indicate how photodynamic therapy could interfere with the development of experimental autoimmune disease, conditions in which activated macrophages are known to be involved.     

Photobiomodulation Enhances Cisplatin Cytotoxicity in a Culture Model with Oral Cell Lineages

Cisplatin plays a central role in cancer chemotherapy, but resistance to this drug remains a major obstacle in treatment. Drawbacks related to cisplatin failure may be associated with cell energy metabolism. This study investigated whether photobiomodulation (PBM) can potentiate the effects of cisplatin on keratinocytes (HaCat) and cancer cells (SCC25 and HN12). Cells were treated with laser (GaAlAs; 660 nm; 60 mW; 0.33 J; 2.14 W cm⁻²; 11.7 J cm⁻² and 6 s) and cisplatin (7.8 μg mL⁻¹) to evaluate cell viability, Ki-67, VEGF, TGF-β1, EGF expression and ROS production. Observations were validated in the SCC25 cell lineage, where the type of cell death (necrosis/apoptosis) and the amount of ATP were assessed. Cell lineages showed increased sensitivity to cisplatin associated with PBM (Cis-PBM). Ki-67 was augmented in all cell lineages treated with Cis-PBM when compared to cisplatin alone (Cis). Cis or Cis-PBM significantly decreased VEGF expression in cancer cells, while no changes were seen in the expression of TGF-β1 or EGF compared to control. ROS levels were similar in the Cis and Cis-PBM groups. Cells treated with Cis-PBM died by apoptosis, leading to greater consumption of ATP. These observations suggest that PBM may potentiate the effects of cisplatin, leading to increased drug cytotoxicity and enhanced cell death.     

Cytotoxic and Photocytotoxic Effects of Cercosporin on Human Tumor Cell Lines

Cercosporin is a naturally occurring perylenequinone. Although other perylenequinones have been extensively studied as photosensitizers in photodynamic therapy of cancer (PDT), cercosporin has been studied in this light only within the remits of phytopathology. Herein, we investigated the photocytotoxicity of cercosporin against two glioblastoma multiforme (T98G and U87) and one breast adenocarcinoma (MCF7) human cell lines. Cercosporin was found to be a potent singlet oxygen producer upon 532 nm excitation, while its cell loading was similar for MCF7 and U87, but approximately threefold higher for T98G cells. The subcellular localization of cercosporin was in all cases in both mitochondria and the endoplasmic reticulum. Light irradiation of cercosporin‐incubated cells around 450 nm showed that T98G cells were more susceptible to cercosporin PDT, mainly due to their higher cercosporin uptake. Metabolic studies before and 1 h following cercosporin PDT showed that cercosporin PDT instigated a bioenergetic collapse in both the respiratory and glycolytic activities of all cell lines. In the dark, cercosporin exhibited a synergistic cytotoxicity with copper only in the most respiratory cell lines (MCF7 and T98G). Cercosporin is a potent photosensitizer, but with a short activation wavelength, mostly suitable for superficial PDT treatments, especially when it is necessary to avoid perforations.     

Nucleosides rich extract from Cordyceps cicadae alleviated cisplatin-induced neurotoxicity in rats: A behavioral,biochemical and histopathological study

This work explored the protective effects of nucleosides rich extract from C. cicadae (CCNE) against cisplatin-induced neurotoxicity. The rats were divided into four groups: normal control (NCA), cisplatin control (CCA), CCNE-L + cisplatin (CCNE-L) and CCNE-H + cisplatin (CCNE-H). The rats in CCNE-L and CCNE-H were orally administered with 100 and 400 mg/kg of CCNE, respectively for five weeks, while the rats in CCA, CCNE-L and CCNE-H groups received intraperitoneal injection of 2.5 mg/kg cisplatin once a week for four weeks starting from the second week of CCNE treatment. After the final treatment, the rats were subjected to behavioural task including Morris water maze test (MWMT), Y maze test, forced swimming (FST), open field test (OFT), rotarod test as well as heat and mechanical hyperalgesia test. Thereafter, the animals were sacrificed and oxidative stress biomarkers, inflammatory mediators and acetylcholinesterase activities were measured in the brain. The histopathological assessment of the brain issues was also performed using H&E staining. The results indicated that CCNE significantly ameliorative cisplatin induced learning and memory impairment (MWMT and Y maze test), depressive behaviours (FST and OFT), motor coordination as well as thermal (hot plate and tail withdrawal test) and mechanical hyperalgesia (von Frey filament test). Furthermore, CCNE decreased acetylcholinesterase level, proinflammatory cytokines levels and lipid peroxidation, with concomitant increase in antioxidant enzymes profiles in the brain tissues of cisplatin treated rats. Additionally, CCNE treatment alleviated histopathological alterations in the brain tissues caused by cisplatin treatment. These results suggested that CCNE ameliorated memory impairment deficits, neuropathy, increased oxidative stress, inflammation in cisplatin treated rats through the inhibition of oxidative stress and inflammation.     

Design,Synthesis, and Molecular Modeling of Asymmetric Tolterodine Derivatives as Anticancer Agents

An efficient and short enantioselective synthesis of (S)‐ and (R)‐tolterodine acid isomers ( 7a – 7i ) was performed a 6‐methyl‐4‐phenylchroman‐2‐one intermediate from inexpensive and commercially available starting materials. A series of tolterodine acid hybrids 7 were synthesized and characterized by infrared, ¹H NMR, ¹³C NMR, X‐ray diffraction, and mass spectral analysis followed by anticancer activity on human cancer cell lines including A549 and SKNSH. Our results revealed the final compounds exhibited moderate to potent activity against A549 and SKNSH. Compounds 7g and 7f were more cytotoxic than cisplatin against all tested two human cancer cell lines, with half maximal inhibitory concentration values of 13.2, 14.3, and 8.5 μM, respectively. In the present investigation, possible binding interaction of the target compounds with 3IVX protein, ligand conformations, including hydrogen bonds and the bond lengths, was analyzed. AutoDock 4.2 chemokine receptor has been investigated by molecular docking and was used to predict the affinity, activity, and binding orientation of ligand with the target protein and to analyze best conformations. Compound 7h exhibited more binding energy (ΔG = −5.52 kcal/mol) and dissociation constant (KI = 89.8 μM) with amino acids Glu 17 and Thr 87 interacting. Further studies are warranted to fully evaluate the analogues as the potential prodrugs with improved physiochemical properties.     

Sun protection Provided by Regulation School Uniforms in Australian Schools: An Opportunity to Improve Personal Sun protection During Childhood

Childhood sun exposure is linked to excessive pigmented mole development and melanoma risk. Clothing provides a physical barrier, protecting skin from ultraviolet radiation (UVR). Extending sleeves to elbow length and shorts to knee length has been shown to significantly reduce mole acquisition in preschoolers from tropical Queensland. We used publicly available uniform images and guidelines from primary schools in Townsville (latitude 19.25°S, n = 43 schools), Cairns (16.87°S, n = 46) and the Atherton Tablelands (17.26°S, n = 23) in tropical Australia to objectively determine the body surface proportion covered by regulation school uniforms. Uniforms of nongovernment, large (≥800 students), urban, educationally advantaged schools with comprehensive sun protection policies covered more skin than those of government schools (63.2% vs 62.0%; P < 0.001), smaller schools (63.4% vs 62.3%; P = 0.009), rural (62.7% vs 61.9%; P = 0.002) and educationally disadvantaged schools (62.8% vs 62.3%; P < 0.001) with underdeveloped sun protection policies (62.8% vs 62.2%; P = 0.002). Overall, SunSmart and non‐SunSmart school uniforms covered identical body surface proportions (62.4%, P = 0.084). Although wearing regulation school uniforms is mandatory at most Australian primary schools, this opportunity to improve children's sun protection is largely overlooked. Recent evidence suggests that even encouraging minor alterations to school uniforms (e.g. slightly longer sleeves/dresses/skirts/shorts) to increase skin coverage may reduce mole acquisition and melanoma risk, especially in high‐risk populations.     

Half‐sandwich ruthenium,rhodium and iridium complexes featuring oxime ligands: Structural studies and preliminary investigation of in vitro and in vivo anti‐tumour activities

Half‐sandwich ruthenium, rhodium and iridium complexes ( 1 – 12 ) were synthesized with aldoxime ( L1 ), ketoxime ( L2 ) and amidoxime ( L3 ) ligands. Ligands have the general formula [PyC(R)NOH], where R = H ( L1 ), R = CH₃ ( L2 ) and R = NH₂ ( L3 ). Reaction of [{(arene)MCl₂}₂] (arene = p ‐cymene, benzene, Cp*; M = Ru, Rh, Ir) with ligands L1 – L3 in 1:2 metal precursor‐to‐ligand ratio yielded complexes such as [{(arene)MLκ²_(N∩N)Cl}]PF₆. All the ligands act as bidentate chelating nitrogen donors in κ²_(N∩N) fashion while forming complexes. In vitro anti‐tumour activity of complexes 2 and 10 against HT‐29 (human colorectal cancer), BE (human colorectal cancer) and MIA PaCa‐2 (human pancreatic cancer) cell lines and non‐cancer cell line ARPE‐19 (human retinal epithelial cells) revealed a comparable activity although complex 2 demonstrated greater selectivity for MIA PaCa‐2 cells than cisplatin. Further studies demonstrated that complexes 3 , 6 , 9 and 12 induced significant apoptosis in Dalton's ascites lymphoma (DL) cells. In vivo anti‐tumour activity of complex 2 on DL‐bearing mice revealed a statistically significant anti‐tumour activity (P  = 0.0052). Complexes 1 – 12 exhibit HOMO–LUMO energy gaps from 3.31 to 3.68 eV. Time‐dependent density functional theory calculations explain the nature of electronic transitions and were in good agreement with experiments.     

Extraction and determination of trace amounts of three anticancer pharmaceuticals in urine by three‐phase hollow fiber liquid‐phase microextraction based on two immiscible organic solvents followed by high‐performance liquid chromatography

An automated three‐phase hollow fiber liquid‐phase microextraction based on two immiscible organic solvents followed by high‐performance liquid chromatography with UV–Vis detection method was applied for the extraction and determination of exemestane, letrozole, and paclitaxel in water and urine samples. n‐Dodecane was selected as the supported liquid membrane and its polarity was justified by trioctylphosphine oxide. Acetonitrile was used as an organic acceptor phase with desirable immiscibility having n‐dodecane. All the effective parameters of the microextraction procedure such as type of the organic acceptor phase, the supported liquid membrane composition, extraction time, pH of the donor phase, hollow fiber length, stirring rate, and ionic strength were evaluated and optimized separately by a one variable at‐a‐time method. Under the optimal conditions, the linear dynamic ranges were 1.8–200 (R² = 0.9991), 0.9–200 (R² = 0.9987) and 1.2–200 μg/L (R² = 0.9983), and the limits of detection were 0.6, 0.3, and 0.4 μg/L for exemestane, letrozole, and paclitaxel, respectively. To evaluate the capability of the proposed method in the analysis of biological samples, three different urinary samples were analyzed under the optimal conditions. The relative recoveries of the three pharmaceuticals were in the range of 91–107.3% for these three analytes.     

A mixed‐ligand copper(II) complex that inhibits growth and induces apoptosis by DNA targeting in human epithelial cervical cancer cells

A new mixed‐ligand copper(II) complex, [Cu(L)(phen)]⋅MeOH (L = 4‐chloro‐2‐[(2‐hydroxyphenyl)iminomethyl]phenol), was synthesized. It belongs to the orthorhombic crystal system and Cu(II) is five‐coordinated in a seriously distorted square pyramidal geometry. DNA binding experiments confirmed an intercalative mode of interaction of the complex with calf thymus DNA. In a DNA cleavage experiment with the complex, as hydrogen peroxide was involved, oxidative DNA cleavage occurred and double‐stranded breaks even appeared at certain concentration. The strong interaction with bovine serum albumin suggested that the complex might be transported by protein. The complex exhibited more significant cytotoxicity in HeLa cells (IC₅₀ = 0.46 ± 0.01 μM) for 48 h, compared with cisplatin (10.61 ± 0.86 μM). This work indicated that the complex could induce apoptosis in a dose‐dependent manner and was associated with cell cycle arrest to some extent. Being consistent with the results of DNA cleavage experiment, comet assay indicated that the complex induced severe DNA fragmentation. The results showed the production of reactive oxygen species increased with increasing concentration of the complex. The complex was suggested to be capable of promoting HeLa cell apoptosis through an oxidative DNA damage pathway.